The purpose of this project is to define the humoral and cellular immune responses that relate to immunopathology, protective immunity and immunodiagnosis of patients with lymphatic filariasis and onchocerciasis. Antibodies of the IgG subclasses appear differentially associated with the clinical manifestations of bancroftian filariasis; patients with elephantiasis have prominent IgG3 antifilarial antibodies and minimal IgG4 responses while the opposite is true for those with asymptomatic infection. These IgG4 antibodies appear to be the "blocking antibodies" responsible for inhibiting IgE-mediated immediate hypersensitivity response in vitro and in vivo, and they have also proven to be useful diagnostically. The eosinophil granule proteins MBP and ECP, important in the pathogenesis of helminth infections, can now be defined in tissues by immunofluorescence (MBP) and in fluids by ELISA with monoclonal antibodies. Populations with bancroftian filariasis or onchocerciasis have been examined to define immunologic parameters that distinguish "naturally" immune from infected individuals. A 43kD protein form infective larvae appears as a potential protective immunogen for bancroftian filariasis, and specific probes are being generated. Enhanced T-cell reactivity to parasite antigen was the marker most clearly distinguishing putatively immune individuals from those with overt onchocerciasis.